A Novel 29-Messenger RNA Host-Response Assay From Whole Blood Accurately Identifies Bacterial and Viral Infections in Patients Presenting to the Emergency Department With Suspected Infections: A Prospective Observational Study

Crit Care Med. 2021 Oct 1;49(10):1664-1673. doi: 10.1097/CCM.0000000000005119.


Objectives: The rapid diagnosis of acute infections and sepsis remains a serious challenge. As a result of limitations in current diagnostics, guidelines recommend early antimicrobials for suspected sepsis patients to improve outcomes at a cost to antimicrobial stewardship. We aimed to develop and prospectively validate a new, 29-messenger RNA blood-based host-response classifier Inflammatix Bacterial Viral Non-Infected version 2 (IMX-BVN-2) to determine the likelihood of bacterial and viral infections.

Design: Prospective observational study.

Setting: Emergency Department, Campus Benjamin Franklin, Charité-Universitätsmedizin Berlin, Germany.

Patients: Three hundred twelve adult patients presenting to the emergency department with suspected acute infections or sepsis with at least one vital sign change.

Interventions: None (observational study only).

Measurements and main results: Gene expression levels from extracted whole blood RNA was quantified on a NanoString nCounter SPRINT (NanoString Technologies, Seattle, WA). Two predicted probability scores for the presence of bacterial and viral infection were calculated using the IMX-BVN-2 neural network classifier, which was trained on an independent development set. The IMX-BVN-2 bacterial score showed an area under the receiver operating curve for adjudicated bacterial versus ruled out bacterial infection of 0.90 (95% CI, 0.85-0.95) compared with 0.89 (95% CI, 0.84-0.94) for procalcitonin with procalcitonin being used in the adjudication. The IMX-BVN-2 viral score area under the receiver operating curve for adjudicated versus ruled out viral infection was 0.83 (95% CI, 0.77-0.89).

Conclusions: IMX-BVN-2 demonstrated accuracy for detecting both viral infections and bacterial infections. This shows the potential of host-response tests as a novel and practical approach for determining the causes of infections, which could improve patient outcomes while upholding antimicrobial stewardship.

Publication types

  • Observational Study

MeSH terms

  • Aged
  • Aged, 80 and over
  • Area Under Curve
  • Bacterial Infections / blood
  • Bacterial Infections / diagnosis*
  • Bacterial Infections / physiopathology
  • Berlin
  • Biomarkers / analysis
  • Biomarkers / blood
  • Emergency Service, Hospital / organization & administration
  • Emergency Service, Hospital / statistics & numerical data
  • Female
  • Humans
  • Male
  • Middle Aged
  • Prospective Studies
  • RNA, Messenger / analysis*
  • RNA, Messenger / blood
  • ROC Curve
  • Virus Diseases / blood
  • Virus Diseases / diagnosis*
  • Virus Diseases / physiopathology


  • Biomarkers
  • RNA, Messenger